Root surface caries is widespread and increasing in adult populations and these lesions show variable ability to remineralize. Neither the mechanism of remineralization, nor the reason for the variability of their remineralization potential is fully understood. The role of phosphoproteins, found in the roots of human teeth, on the remineralization potential of root caries lesions has not been investigated. Although more extensively studied, the role of phosphoprotein in biological mineralization is also not understood. Therefore, this study will first examine the role of phosphoprotein in remineralization; however, because of the close association between these two processes, the data generated in the study should provide information on biomineralization as well. Three observations have been made that may have important clinical implications on the ability of root surfaces to remineralize in the oral cavity. First, there are two pools of phosphoprotein in human tooth roots, a soluble pool that is easily removed by 10% EDTA demineralization and an insoluble pool that is only recovering using collagenase digestion. Second, phosphoprotein is degraded during the mineralization and maturation process. Thirdly, the soluble degraded phosphoprotein acts as an inhibitor of the remineralization of demineralized mature human root organic matrices. Despite the importance of these observations, further studies are needed to clarify the roles of the various phosphoproteins in remineralization and biomineralization. Therefore, intact and degraded, soluble and insoluble phosphoprotein will be extracted, isolated and purified from the organic matrices of demineralized human root shards and sections. These proteins will be stabilized within organic matrices and attached to agarose beads and then be exposed to metastable remineralization solutions. The ability of these substrates to mineralize will be examined by TEM and microradiography. The recent isolation of an intact 96K phosphoprotein from human immature roots will allow for the first time an immunocytochemical study which will allow the distribution of the phosphoprotein and its relationship to mineral deposition (nucleation) to be determined. Monoclonal and polyclonal antibodies will be raised to the soluble and insoluble phosphoprotein and western immunoblotting will be used to determine the cross-reactivity of the resulting antibodies with intact and degraded, soluble and insoluble phosphoprotein. A novel in vivo approach will be taken to examine the effects of the phosphoprotein using an intraoral appliance. Partially and fully demineralized matrices with and without soluble phosphoprotein will be placed into the appliance and the effects of the protein on remineralization investigated intraorally. In addition, an optimized remineralization gel and solution will be tested to determine their potential as a preventive and/or treatment therapy for root surface lesions.